In a recently completed study, we found that in rats that received programmed infusions of 1 mg/kg cocaine every 12 min for 2 hr over 10 days, the pre-infusion concentrations of prolactin (PRL) increased in a time-dependent manner whereas post-infusion levels of PRL were decreased by cocaine. Because dopamine (DA) and PRL are reciprocally related in male rats, these changes could involve modification of the release of DA from hypothalamic tuberoinfundibular neurons. We are testing this hypothesis in rats treated as described above for 9 days with cocaine or saline. On the 10th day, the hypothalamo-hypophysial portal blood will be collected for 30 min before the initiation of passive infusions of cocaine or saline, during 60 min of intermittent infusion, and for 30 min following a challenge of amphetamine. Arterial blood will be collected concurrently. These aliquots will be assayed in Dr. Mefford's laboratory using microbore high performance liquid chromatography. If there are differences between cocaine- and saline-treated animals, another series will be performed with lidocaine as the infusate as a control for the local anesthetic effects of cocaine. This experiment will provide the first evidence of cocaine-induced modifications of functional DA release coupled to a physiological relevant event, the release of PRL, and can serve as a model of the action of cocaine on other central DA systems.